Causal Relationship Between Sleep Traits and Risk of Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study

Abstract

A correlation between sleep and systemic lupus erythematosus (SLE) has been observed in a number of prior investigations. However, little is known regarding the potential causative relationship between them. In this study, we selected genetic instruments for sleep traits from pooled data from published genome-wide association studies (GWAS). Independent genetic variants associated with six sleep-related traits (chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, and daytime sleepiness) were selected as instrumental variables. A two-sample Mendelian randomization (TSMR) study was first conducted to assess the causal relationship between sleep traits and SLE (7219 cases versus 15,991 controls). The reverse MR analysis was then used to infer the causal relationship between SLE and sleep traits. Inverse variance weighted (IVW), MR Egger, Weighted median, and Weighted mode were applied to perform the primary MR analysis. MR Egger regression and the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test were used to detect horizontal pleiotropy, and Cochran’s Q was used to detect heterogeneity. In studies of the effect of sleep traits on SLE risk, the IVW method demonstrated no causal relationship between chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, daytime sleepiness and SLE risk. The remaining three methods agreed with the results of IVW. In studies of the effect of SLE on the risk of sleep traits, neither IVW, MR Egger, Weighted median, nor Weighted mode methods provided evidence of a causal relationship between SLE and the risk of sleep traits. Overall, our study found no evidence of a bidirectional causal relationship between genetically predicted sleep traits and SLE.

Assessment of bidirectional relationships between systemic lupus erythematosus and anxiety disorder: A two-sample Mendelian randomization study

“…The F statistic is calculated as F = R 2 (n-k-1)/[k (1-R 2 )]. 21 In addition, we remove the SNP directly associated with the outcome by searching on the PhenenoScanner website (https://www.phenoscanner.medschl.cam.ac.uk/).…”

“…All IVs need to avoid weak instrument bias in MR analysis, that is, the F statistic of IV should be greater than 10. The F statistic is calculated as 21 In addition, we remove the SNP directly associated with the outcome by searching on the Phene-noScanner website (https://www.phenoscanner.medschl. cam.ac.uk/).…”

Circadian rhythm in systemic autoimmune conditions: Potential of chrono-immunology in clinical practice: A narrative review

“…[12] However, a recent study did not establish a causal relationship between genetically predicted traits (e.g., chronotype, sleep duration, insomnia, and daytime sleepiness) and SLE. [26] Rather, sleep deprivation has been shown to accelerate autoantibody production in mice, [27] which could be related to the disease's progression.…”

Association between sleep traits and primary liver cancer: A Mendelian randomization analysis

“…These can cause different kinds of diseases including Parkinson's disease, cardiovascular disease, cerebrovascular disease, systemic lupus erythematosus and various types of cancers. [5][6][7][8][9] Therefore, researchers are dedicated to the work of sleep traits and their effects on cancers. Emerging evidence suggests that sleep may play a crucial role in cancer, particularly in breast cancer [10][11][12][13] and lung cancer.…”